Imaging of Cancer Cells and Dictated Cytotoxicity Using Aptamer-Guided Hybridization Chain Reaction (HCR)-Generated G-Quadruplex Chains

DNA nanotechnology provides powerful tools for developing cancer theranostics. Here we introduce the autonomous surface-nucleolin-guided HCR that leads to the polymerization of G-quadruplex polymer chains, in which the Zn-II-protoporphyrin IX is intercalated. We demonstrate that MDA-MB-231 (Triple Negative Breast Cancer cells, TNBC) with overexpressed surface nucleolin were able to induce HCR leading to the formation of the Zn-II PPIX-loaded G-quadruplex polymer chains, while the M10 epithelial breast cells served as control. The Zn-II PPIX-loaded nanowires allow the selective imaging of TNBC, and their permeation into the TNBC leads to selective cytotoxicity and guided photodynamic therapy toward the cancer cells due to structural perturbation of the membranes. The aptamer-guided HCR-generated G-quadruplex polymer chains may serve as a versatile tool to target TNBC featuring poor prognosis and high pathological risk of recurrence, thus offering a promising theranostic platform.